Endometrial cancer (EC) is the 6th most common and the 14th most deadly cancer among women worldwide; however, outcomes remain poor for women with advanced-stage or recurrent disease. Substantial research is currently being conducted on molecular mechanisms of endometrial carcinogenesis with the goal of creating new therapeutic strategies for overcoming chemotherapy resistance. Initially classified as either type I or type II tumors, analysis of The Cancer Genome Atlas has led to a reorganization of EC into four groups based on molecular characteristics, with studies ongoing to determine the prognostic and therapeutic significance of this schema. The role of Wnt signaling in EC has been demonstrated in multiple studies and is believed to mediate the proliferative influence of estrogen on endometrial tissue. Current therapies in phase I/II clinical trials for solid tumors include several small-molecule inhibitors of the canonical Wnt pathway, a Porcupine inhibitor, a Wnt5A mimetic, an ROR1 antibody, and an ROR1 CART-cell therapy. Alterations in PI3K-AKT-mTOR signaling, especially via PTEN mutations, are common in type 1 EC, making this pathway an attractive target for molecular therapy. Temsirolimus, everolimus, and ridaforolimus have all been evaluated in phase I/II clinical trials, where they have proven most effective in treatment-naïve patients and as adjuncts to front-line therapy. Second-generation mTORC1/2 inhibitors, PI3K inhibitors, dual mTOR/PI3K inhibitors, and AKT inhibitors are also in early-phase clinical trials. Metformin has shown an intriguing ability to reverse hyperplasia in conjunction with progestogens and to prevent the recurrence of AEH and EC, making it an attractive option for patients desiring fertility preservation. Due to the significance of angiogenic growth factors in EC, several agents targeting multiple upstream receptor tyrosine kinases within the EGFR/FGF-Ras-Raf-MEK-ERK signaling pathway are currently in clinical trials, including brivanib, nintedanib, dovitinib, lenvatinib, and ponatinib. Of these, dovitinib and lenvatinib have shown the most promising results. Hypoxia and triggered angiogenesis are critical, but understudied, components of tumorigenesis in EC. Bevacizumab is the best-studied antiangiogenic agent, with moderate activity seen when used as a single agent and more promising results obtained by combining it with front-line therapies. Going forward, robust molecular screening tools are needed for both improved patient selection and identification of prognostic biomarkers, and further study with more selective agents is warranted to parse out the isolated impact of tyrosine kinase inhibition and antiangiogenic agents in recurrent EC.
Pregnant women are at increased risk for severe morbidity and mortality due to respiratory infections like SARS-CoV-2 (COVID-19) during pregnancy1. Those with substance use disorders (SUD) may be especially vulnerable due to high rates of smoked tobacco, cannabis and methamphetamine use which adversely affect pulmonary function.2 However, little is known about differential effects of COVID-19 on pregnant women with and without SUD.This was a retrospective cohort study of commercially insured pregnant women ages 15-44 using national administrative healthcare data from Optum’s deidentified Clinformatics® Data Mart Database version 8.1 (2007-2020). Women with a delivery hospitalization between January 1, 2020-August 19, 2020 continuously enrolled in insurance for ≥8 weeks during pregnancy and 6 weeks postpartum were included. SUD was defined using ICD-10 diagnoses for ≥ 1 SUD during pregnancy including alcohol, amphetamine, cannabis, cocaine, opioid or other substance use disorder.3 COVID-19 screening and diagnosis were defined using ICD-10 coding and reporting guidelines published by the CDC.4, 5 We used T-tests, Fisher’s exact tests, and quantile regression (percentiles) to examine statistical differences. This study was exempt by the University of Pittsburgh IRB because deidentified healthcare data were used.Among 65,009 pregnancies, 2,616 (4.0%) had ≥1 SUD diagnosis. Almost half of the pregnant women in the cohort were non-Hispanic White (48%) and most lived in the South (41%) or the Midwest (28%) region of the United States (Table). Pregnant women with an SUD diagnosis were significantly more likely to be younger (30±6 vs 32±5; p<.05). Compared with the overall sample, non-Hispanic Black (10% vs 7%; p,.05) and non-Hispanic White (54% vs 48%; p<.05) women were overrepresented among those with SUD as opposed to Hispanic and non-Hispanic Asian women. Overall, 27% of pregnant women were screened and evaluated for COVID-19 during pregnancy or postpartum. Women without an SUD diagnosis were significantly more likely to be screened for COVID-19 during pregnancy (27% vs 24%; p<0.001) than those with an SUD. Overall, 3.4% of pregnant women were diagnosed with COVID-19, mostly (86%) in the third trimester. The prevalence of a COVID-19 diagnosis was higher among those with a SUD compared to those without an SUD (5% vs 3%; p<0.05). Further, there was a higher percentage of COVID-19 related hospitalizations among pregnant women with an SUD (36%) than those without an SUD (8%) (p<0.001). The median length of stay was one day longer among those with a SUD (3 vs 2 days; p<0.01) compared to those without an SUD. There were no COVID-19 related deaths reported during pregnancy or postpartum.In this national cohort, pregnant women with a SUD had a higher COVID-19 diagnosis rate than those without a SUD, despite lower screening rates. Among those with a COVID-19 diagnosis, pregnant women with a SUD had a significantly higher rate of COVID-19 related hospitalizations and longer median length of stay than those without a SUD. Efforts to improve COVID-19 screening rates and decrease morbidity associated with COVID-19 diagnosis among pregnant women with SUDs may be warranted.
Objective. To survey the opinions of adolescent health care providers regarding the availability of over-the-counter (OTC) oral contraceptives (OCs) to adolescents and whether this intervention may decrease the number of unintended adolescent pregnancies.Methods: Academic hospitals, neighborhood health centers, and family planning centers in the city of Boston were contacted. The health care providers who were most involved in adolescent contraceptive counseling were surveyed.Results: Forty-nine providers participated. Ninety percent of providers (44 of 49) were against making OCs available OTC to adolescents. Seventy-three percent did not think that OTC OCs would decrease the number of unintended adolescent pregnancies.Conclusions: Our survey shows that adolescent health care providers surveyed in Boston are opposed to making OCs available to adolescents over the counter. The majority do not think this would decrease the number of unintended adolescent pregnancies. The providers predicted that without the interactive counseling provided by clinicians, adolescents would be unlikely to utilize OCs effectively. Additionally, adolescents would be seen less for sexually transmitted diseases (STDs) screening and other routine health care.
Previous research has demonstrated that the sisters of adolescent mothers have an increased risk of becoming teenage parents. From our experience in caring for over 600 teenage mothers in a comprehensive family-oriented teen-tot clinic, we have developed a conceptual model, based on social cognitive theory, which describes the influence of teenage mothers on their sisters' decisions about pregnancy and childbearing. Our model focuses on the direct effects of both intrafamilial and social-cultural factors on adolescents' childbearing attitudes and their individual sexual values. Intrafamilial factors include the impact of sibling teenage parents and influences of parenting styles. Social-cultural factors include social norms that favor early sexual behavior and childbearing. These interact with peer influence to directly affect social and self-regulative skills, feeling of self-efficacy, and the individual's sexual values. Personal factors, such as hopelessness and depression, are influenced by multigenerational poverty. These personal factors are integrated with intrafamilial and social-cultural factors to produce the adolescent's personal meaning and cognitive assessment of pregnancy and childbearing. Clinicians can use this model when developing interventions that focus on the various factors that influence an adolescent sister's decisions about becoming pregnant.
HPC processing has been performed routinely for many years for the preparation and cryopreservation of HPC used for autologous and allogeneic transplantation. JACIE Standards (section D) regulate HPC processing and request that processing is performed within the framework of a quality management system (QMS). Implementing QMS in HPC-processing laboratories is feasible, and many processing laboratories are already accredited according to various standards.Before hematopoietic stem cell transplantation, it is recommended that accurate quality controls be performed to assess the median number of viable CD45+/7-aminoactinomycin-d (7-AAD) and CD45+/CD34+/7-AAD cells, the presence of microbiologic contamination, and the proliferative potential of hematopoietic progenitor cells. The guidelines for the determination of the QCs have been established by FACT/JACIE standards.To be optimal, process and quality controls have to be performed in a real-time manner in order to ensure safe product release and an immediate recognition of deviations. Furthermore, the immediate initiation of corrective measures is crucial for risk prevention.
